Reaction mass of L-Glutamic acid, N-coco acyl derivs., monosodium salts and sodium hydrogen N-(1-oxooctadecyl)-L-glutamate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 January 2013 to 13 February 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with GLP and agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Remarks:

Study conducted on read-across material

Justification for type of information:

A RAAF report will shortly be provided.

Cross-reference

Reason / purpose for cross-reference:

other: Read-across target

Reference

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted on read-across material

Justification for type of information:

A RAAF report will shortly be provided.

Reason / purpose for cross-reference:

read-across source

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of sodium hydrogen N-(1-oxooctadecyl) -L-glutamate and sodium hydrogen n-(1-oxohexadecyl) -L-glutamate

IUPAC Name:

Reaction mass of sodium hydrogen N-(1-oxooctadecyl) -L-glutamate and sodium hydrogen n-(1-oxohexadecyl) -L-glutamate

Test material form:

solid: particulate/powder

Details on test material:

- Appearance: White to pale yellow powder
- Storage conditions of test material: Room temperature (15-25 °C)

Test animals

Species:

rat

Strain:

other: CRL:(WI) (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adults
- Weight at study initiation: 219 to 248 g
- Housing: Individually in type II polypropylene/polycarbonate cages
- Diet: ad libitum
- Water: municipal tap water ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 to 70 % (relative)
- Air changes: 15 to 20 air changes per hour
- Photoperiod: 12 hour light/dark cycle (light from 06:00 to 18:00)

IN-LIFE DATES:
From: 24 January 2013
To: 13 February 2013

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Back. Animals were shaved 24 hours prior to exposure
- % coverage: Approximately 10 %
- Type of wrap if used: Sterile gauze pads held in place by a patch with an adhesive hypoallergenic plaster and the entire trunk of the animal wrapped in a semi-occlusive plastic wrap.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Water (at body temperature)
- Time after start of exposure: 24 hours

TEST MATERIAL
- For solids, paste formed: Yes; the test material was moistened with water to ensure good contact with the skin

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were performed on the day of treatment at 1 and 5 hours after application and once each day thereafter. Observations included the skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. Body weights were recorded on Day 0 (prior to test material administration), and on days 7 and 14.
- Necropsy of survivors performed: Yes. All animals were anaesthetised with RELEASE 300 mg/mL inj. A.U.V and exsanguinated. After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed. All macroscopic changes were recorded.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: No clinical signs, including local dermal signs, were observed after treatment with the test material or during the 14-day observation period.

Gross pathology:

There was no evidence of any macroscopic changes at necropsy.

Any other information on results incl. tables

Table 1: Bodyweight and Bodyweight Gain for Males

Animal No.	Bodyweight (g)			Bodyweight Gain (g)
	Day 0	Day 7	Day 14	Days 0 to 7	Days 7 to 14	Days 0 to 14
9419	237	292	333	55	41	96
9420	248	292	334	44	42	86
9421	245	287	313	42	26	68
9422	234	281	329	47	48	95
9423	234	284	334	50	50	100
Mean	239.6	287.2	328.6	47.6	41.4	89.0
Standard Deviation	6.5	4.9	9.0	5.1	9.4	12.8

 

Table 2: Bodyweight and Bodyweight Gain for Females

Animal No.	Bodyweight (g)			Bodyweight Gain (g)
	Day 0	Day 7	Day 14	Days 0 to 7	Days 7 to 14	Days 0 to 14
9424	230	252	262	22	10	32
9425	227	256	272	29	16	45
9426	243	260	273	17	13	30
9427	220	240	275	20	35	55
9428	219	232	251	13	19	32
Mean	227.8	248.0	266.6	20.2	18.6	38.8
Standard Deviation	9.7	11.7	10.1	6.0	9.8	10.8

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute dermal median lethal dose (LD50) was determined to be > 2000 mg/kg bw in male and female rats.

Executive summary:

The acute dermal toxicity of the test material was determined in male and female CRL:(WI) rats in accordance with the standardised guideline OECD 402 under GLP conditions.

The study was performed as a limit test. 2000 mg/kg bw was applied to the shaved back of 5 animals of each sex (equating to around 10 % of the surface area of the skin) and covered with a semi-occlusive dressing. After 24 hours, the test site was washed with water and the animals were observed for any reactions over a fourteen day observation period. Bodyweights were recorded at days 0, 7 and 14. At the end of the study, all surviving animals were submitted for necropsy.

There was no mortality throughout the study and none of the animals demonstrated any clinical signs of toxicity. Bodyweights and bodyweight gains were not affected by test material administration. All animals were found to be normal at necropsy.

Under the conditions of this study, the acute dermal median lethal dose (LD50) was determined to be > 2000 mg/kg bw in male and female rats.